PROJECT SUMMARY/ABSTRACT Funds are requested to purchase a JEM-1400 Plus transmission electron microscope (TEM) to continue to meet the ongoing and future demands of numerous researchers within the School of Medicine and general campus at UCSD. The requested TEM has an objective lens configuration optimized for high contrast microscopy of biological samples and is perfectly suited for imaging conventional ultrathin plastic sections, immunogold labeled ultrathin cryosections, and negatively stained samples. The JEM-1400 Plus system is particularly adaptable to the diverse group of users and the multi-user environment constituted by our TEM Core Facility. Our existing 26 year old instrument, a JEOL 1200-EX2, is showing clear signs of wear and is plagued by increasing down time due to the age and past usage of the instrument. Future reliability is a major concern, and we are seeking to replace this TEM with a modern, state-of-the-art instrument. Our users study a variety of projects, ranging from use of nanoparticles in biomedical research to fine structure and immunolocalization of cells and molecules involved in cardiovascular and neurological diseases and cancer. All have in common that they center on cell biological questions that require ultrastructural analysis and/or immunolocalization studies. The new TEM will ensure that our group of outstanding users have continued and uninterrupted access to the techniques and applications necessary for state-of-the-art research in these fields. The JEM-1400 Plus will be located, administered and maintained in the existing CMM TEM Core facility?a shared resource that is utilized regularly by numerous researchers. The new TEM will be included in the existing cost recovery system to ensure partial recovery of funds for salaries, maintenance agreements and supplies.